1. Field of the Invention
This invention relates generally to systems for performing optical sensing, and more particularly to micro-machined electrical-optical-mechanical systems for high-resolution chemical and biological sensing applications.
2. Background
Recent advances in processes for micro-machining silicon have made it possible to implement complete micro-machined electrical-optical-mechanical systems (MEOMS) on a chip. For example, MEOMS have recently been developed that incorporate sensors for detecting substances and measuring related physical properties. An important advantage of such MEOMS is the ability to place interfaces, sensors, and signal processing circuitry on the same silicon substrate, thereby making these systems high speed, portable, and relatively low cost.
A traditional method of detecting chemical and biological substances and measuring related physical properties, which may be implemented as part of a MEOMS, involves an optical technique known as evanescent wave surface detection. Generally, evanescent wave surface detection includes applying a fluid sample to the surface of a waveguide. Frequently, the waveguide surface is coated with a chemically sensitive layer and the fluid sample is allowed to react with this layer. Next, light is coupled into the waveguide, and the light propagating through the waveguide causes evanescent wave fields to be produced that reach out into the fluid sample on the waveguide surface. Because the fluid sample applied to the waveguide surface changes the effective index of refraction of the waveguide, the light propagating through the waveguide undergoes a shift in phase. Accordingly, the fluid sample on the waveguide surface can be detected and properties relating to the fluid sample can be measured by measuring the phase shift of the light coupled out of the waveguide.
One optical technique for detecting chemical and biological substances that uses evanescent wave surface detection is disclosed in U.S. Pat. No. 5,120,131 issued Jun. 9, 1992 to Lukosz. That patent discloses a technique that includes applying a fluid sample to a waveguide surface and then coupling light into the waveguide, thereby causing evanescent wave fields to reach out into the fluid sample. Specifically, the light coupled into the waveguide is polarized so that it propagates through the waveguide as two mutually coherent and orthogonally polarized modes. This is because the penetration depths of the evanescent wave fields corresponding to the two modes are different, thereby causing the modes propagating through the waveguide to undergo different amounts of phase shift. The fluid sample on the waveguide surface is therefore detected and its properties are measured by measuring differences in the phase shifts, xcex94"PHgr", for the two orthogonal modes.
Although this optical technique has been successfully used for detecting chemical and biological substances and measuring related physical properties, it has some drawbacks. For example, the phase difference of the two orthogonal modes can at best be determined with a resolution of xcex4(xcex94"PHgr")xe2x89xa62xcfx80/1000, which is generally not good enough for detecting extremely small chemical and biological substances in the fluid sample. Biochemical and environmental factors such as non-specific binding and temperature variation in the fluid sample further limit the resolution of this optical technique.
Another optical technique that uses evanescent wave surface detection is disclosed in U.S. Pat. No. 5,262,842 issued Nov. 16, 1993 to Gauglitz et. al. That patent discloses an integrated optical Mach-Zehnder interferometer fabricated on a substrate. The interferometer includes a single mode waveguide structure for bifurcating a beam of light into two separate optical paths, which include a measurement path and a comparison path. The surface of the measurement path can be coated with a chemically sensitive layer and a fluid sample allowed to react with this layer. After propagating through the measurement and the comparison paths, the bifurcated light beams are then recombined. Because the chemically sensitive layer changes the index of refraction of the measurement path, the light beam propagating within the measurement path experiences a phase shift. As a result, interference between the two light beams can be measured in the recombined beam. Significantly, this measured interference is proportional to the quantity of chemical or biological substance in the fluid sample.
Although this optical technique including a measurement path and a comparison path has the advantage of effectively canceling out non-specific binding and temperature variation in the fluid sample, it also has drawbacks in that the resolution of the technique is generally insufficient for detecting extremely small chemical and biological substances in the fluid sample.
Not only is it desirable to have a MEOMS with high resolution sensors for detecting extremely small chemical and biological substances in fluid samples, but it is also desirable to have a MEOMS with structure that supports the testing of extremely small quantities of fluid samples. One such structure is disclosed in International Publication WO 98/28075 published Jul. 2, 1998 to Imaging Research Inc., St. Catharines, Ontario, Calif. That publication discloses a micro-well plate designed for use in imaging systems for imaging of fluorescent, chemiluminescent, bioluminescent, and colorimetric assays. Specifically, the publication discloses structure for optimizing the optical properties of the micro-wells, which are designed to hold extremely small quantities of fluid sample.
International Publication WO 98/46981 published Oct. 22, 1998 to LJL Biosystems, Sunnyvale, Calif., USA, discloses another micro-well plate design that further reduces the quantity of fluid sample required for successful imaging.
However, neither International Publication WO 98/28075 nor WO 98/46981 disclose structure for controlling the transfer of extremely small quantities of fluid sample into and out of the micro-wells. We have recognized that a practical MEOMS incorporating high-resolution chemical and biological sensors must include such structure.
It would therefore be desirable to have a MEOMS for chemical and biological sensing applications. Such a MEOMS would include high-resolution chemical and biological sensors that are capable of detecting extremely small chemical and biological substances in a fluid sample. It would also be desirable to have a MEOMS for chemical and biological sensing applications that includes structure for holding extremely small quantities of the fluid sample and for controlling the transfer of the fluid sample into and out of the MEOMS.
The foregoing drawbacks of the prior art have been overcome by an MEOMS sensing chip according to the present invention. In a preferred embodiment, the MEOMS sensing chip includes a system for optically sensing substances in fluid samples and a system for delivering the fluid samples to the sensing system, wherein the sensing system includes at least one two-branch waveguide and a plurality of ring waveguides, each branch of the two-branch waveguide being used for coupling light energy into one of the plurality of ring waveguides, wherein the delivering system includes a plurality of micro-channels and a plurality of micro-wells, the micro-channels being used for transporting the fluid samples to the micro-wells, each micro-well being aligned with a respective ring waveguide and being used for exposing the fluid sample therein to the respective ring waveguide, and wherein characteristics related to the coupling of the light energy into the plurality of ring waveguides are used for detecting substances in the fluid samples.
In another embodiment, a device for optically sensing substances in fluid samples includes a first channel waveguide for coupling light energy into a first ring waveguide, the first ring waveguide having a test sample applied to a surface thereof, a second channel waveguide for coupling light energy into a second ring waveguide, the second ring waveguide having a reference sample applied to a surface thereof; a laser for injecting light into the first and the second channel waveguides; and, at least one detector for measuring the intensities of light coupled out of the first and the second channel waveguides, wherein the intensity measurements are used for sensing substances in the test sample relative to the reference sample.
In still another embodiment, a method for optically sensing substances in fluid samples includes exposing a test sample to a first ring waveguide; injecting a light beam into a first channel waveguide, thereby coupling at least a portion of the light beam energy into the first ring waveguide; and, detecting the intensity of a remaining portion of the light beam energy coupled out of the first channel waveguide, wherein the detected energy is indicative of the presence of a substance in the test sample.
Other aspects of the invention are disclosed infra.